Mechanical Force Inhibits Osteoclastogenic Potential of Human Periodontal Ligament Fibroblasts Through OPG Production and ERK-Mediated Signaling
Mechanical Force Inhibits Osteoclastogenic Potential of Human Periodontal Ligament Fibroblasts Through OPG Production and ERK-Mediated Signaling
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DOI：
10.1002/jcb.22086
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发表时间：
2009-04-15
影响因子：
4
通讯作者：
Lee, Jeong-Chae
中科院分区：
文献类型：
--
作者：
Kook, Sung-Ho;Son, Young-Ok;Lee, Jeong-Chae
牙周韧带和牙龈成纤维细胞在骨重塑中起重要作用。牙周韧带成纤维细胞刺激骨重塑，牙龈成纤维细胞保护异常骨吸收。然而，很少有研究检查了两种成纤维细胞群体之间刺激破骨细胞形成的差异。机械力对这些种群的破骨细胞形成的确切影响也是未知的。本研究发现，骨髓细胞与牙周韧带共培养诱导的破骨细胞样细胞多于牙龈成纤维细胞，且在共培养中加入抗骨保护素（OPG）抗体后，破骨细胞样细胞数量显著增加。在地塞米松和维生素D-3的共同作用下，两种人群的核因子- κ b配体受体激活因子（RANKL） mRNA水平均升高。离心力抑制了两个种群的破骨细胞生成，这可能与力诱导的OPG上调有关。通过药理学抑制剂（10 μ M PD98059）或siERK转染抑制细胞外信号调节激酶（ERK）信号，抑制力诱导的OPG上调，同时增加因力而减少的破骨细胞样细胞。这些结果表明，牙周韧带成纤维细胞天生比牙龈成纤维细胞更擅长诱导破骨细胞，离心力通过OPG的产生和ERK的激活抑制牙周成纤维细胞的破骨发生。j .细胞。生物化学学报，26(6):1010-1019,2009。(c) 2009 Wiley-Liss, Inc。
Periodontal ligament and gingival fibroblasts play important roles in bone remodeling. Periodontal ligament fibroblasts stimulate bone remodeling while gingival fibroblasts protect abnormal bone resorption. However, few studies had examined the differences in stimulation of osteoclast formation between the two fibroblast populations. The precise effect of mechanical forces on osteoclastogenesis of these populations is also unknown. This study revealed that more osteoclast-like cells were induced in the co-cultures of bone marrow cells with periodontal ligament than gingival fibroblasts, and this was considerably increased when anti-osteoprotegerin (OPG) antibody was added to the co-cultures. mRNA levels of receptor activator of nuclear factor-kappaB ligand (RANKL) were increased in both populations when they were cultured with dexamethasone and vitamin D-3. Centrifugal forces inhibited osteoclastogenesis of both populations, and this was likely related to the force-induced OPG up-regulation. Inhibition of extracellular signal-regulated kinase (ERK) signaling by a pharmacological inhibitor (10 mu M PD98059) or by siERK transfection suppressed the force-induced OPG up-regulation along with the augmentation of osteoclast-like cells that were decreased by the force. These results suggest that periodontal ligament fibroblasts are naturally better at osteoclast induction than gingival fibroblasts, and that centrifugal force inhibited osteoclastogenesis of the periodontal fibroblasts through OPG production and ERK activation. J. Cell. Biochem. 106: 1010-1019, 2009. (c) 2009 Wiley-Liss, Inc.